- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Ghosh, S., Ghosh, S., Mansi, M., Long, X., Clark, L., Srivastava, A., Kakkunath, S., Orosa-Puente, B., Bailey, M., Bhagat, P. K., Gough, C., Zhang, C., de Lucas, M., Sadanandom, A.It has long been observed that light perception by phytochromes control plant immunity, however, the underpinning molecular mechanism is less well understood. We demonstrate that light mediated SUMO conjugation to Phytochrome B (PhyB) is critical for increasing cellular salicylic-acid (SA) levels to orchestrate systemic acquired resistance (SAR) upon avirulent bacterial infection. SUMOylation is critical for PhyB nuclear condensate formation during light activated immunity. Light induced PhyB SUMOylation recruits NPR1, through its SUMO interacting motif to nuclear condensates to elevate SA […]
- by Gu, A., Chen, J. Y.Identifying actionable drug targets is a critical challenge in cancer research, where high-dimensional genomic data and the complexity of tumor biology often hinder effective prioritization. To address this, we developed GETgene-AI, a novel computational framework that integrates network-based prioritization, machine learning, and automated literature analysis to identify and rank potential therapeutic targets. Central to GETgene-AI is the G.E.T. strategy, which combines three data streams: mutational frequency (G List), differential expression (E List), and known drug targets (T List). These components […]
- by Mora Carrera, E., Yousefi, N., Potente, G., Stubbs, R. L., Keller, B., Leveille-Bourret, E., Stefan, G., Celep, F., Giorgi, T., Conti, E.Despite the evolutionary importance of supergenes, their properties in polyploids remain unexplored. Polyploid genomes are expected to undergo chromosomal rearrangements and gene losses over time, potentially affecting supergene architecture. The iconic distyly supergene (S-locus), controlling a floral heteromorphism with two self-incompatible morphs, has been well-documented in diploids, but remains unknown in polyploids. Primula, the classic model for distyly since Darwin, is ancestrally diploid and distylous, yet polyploid, homostylous species with a single, self-compatible floral morph evolved repeatedly. The intraspecific loss […]
- by Oudyk, K. M., Dockes, J., Peraza, J. A., Kent, J., Torabi, M., Wang, M., McPherson, B. C., Mirhakimi, N., de la Vega, A., Laird, A., Poline, J.-B.Meta-analyses are invaluable tools for navigating the rapidly expanding scientific literature. Given their high value, ensuring the quality of meta-analyses is paramount. We conducted a multifaceted overview, examining each step in a manual neuroimaging meta-analysis on a large scale. We used four novel datasets comprising over 14,000 papers, including fMRI meta-analyses, fMRI studies, studies included in meta-analyses, and studies associated with image data on NeuroVault. Regarding successes, two-thirds of meta-analyses stated that they followed PRISMA guidelines, and 65% included a […]
- by Brochard, S., Vanlaeys, A., Taieb, M., Richard, I., Aury-Landas, J., Bernay, B., Pontin, J., Seillier, C., Bon, N., Picart, B., Pecqueur, C., Toutirais, O., Vinatier, C., Guicheux, J., Maubert, E., Agin, V., Boumediene, K., Bauge, C.Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, has gained attention as a promising therapeutic target in osteoarthritis (OA) due to its central role in modulating inflammation, catabolism, and hypertrophy within chondrocytes. Previous studies have further demonstrated that EZH2 inhibition can slow OA progression in surgically induced mouse models, highlighting its potential in reducing joint degradation. However, the precise mechanisms by which EZH2 influences other key cell types in OA pathology remain poorly understood. In this study, we aimed […]
- by Cesar, C. S., Miranda, V. H., Silveira, E. R., de Oliveira, T. A., Cogni, R.Organisms are constantly at risk of being infected by pathogens such as viruses. Adaptations against viral infection include immune defenses encoded within the host genome and associations with defensive symbionts such as Wolbachia. Wolbachia is widely spread among insects, and its success in nature may be due to its antiviral effects, which can benefit hosts if viruses significantly reduce host fitness. Here, we conducted a meta-analysis to assess the degree to which viral infection affects the fitness of insect hosts, […]
- by Peng, S., Li, C., Wang, Y., Yi, Y., Chen, X., Yin, Y., Yang, F., Chen, F., Ouyang, Y., Xu, H., Chen, B., Shi, H., Li, Q., Zhao, Y., Feng, L., Gan, Z., Xie, x.Accumulating evidence indicates that metabolic enzymes can directly couple metabolic signals to transcriptional adaptation and cell differentiation. Glycogen synthase 1 (GYS1), the key metabolic enzyme for glycogenesis, is a nucleocytoplasmic shuttling protein compartmentalized in the cytosol and nucleus. However, the spatiotemporal regulation and biological function of nuclear GYS1 (nGYS1) microcompartments remain unclear. Here, we show that GYS1 dynamically reorganizes into nuclear condensates under conditions of glycogen depletion or transcription inhibition. nGYS1 complexes with the transcription factor NONO/p54nrb and undergoes liquid-liquid […]
- by Apte, A., LoCastro, E., Iyer, A., Elguindi, S., Jiang, J., Oh, J. H., Veeraraghavan, H., Dave, A., Deasy, J. O.This work introduces a user-friendly, cloud-based software framework for conducting Artificial Intelligence (AI) analyses of medical images. The framework allows users to deploy AI-based workflows by customizing software and hardware dependencies. The components of our software framework include the Python-native Computational Environment for Radiological Research (pyCERR) platform for radiological image processing, Cancer Genomics Cloud (CGC) for accessing hardware resources and user management utilities for accessing images from data repositories and installing AI models and their dependencies. GNU-GPL copyright pyCERR was […]
- by Xiong, C., Huang, S., Zhou, M., Zhang, Y., Wu, W., Li, X., Yao, H., Chen, J., Li, Y.Spatial transcriptomics (ST) data, by providing spatial information, enables simultaneous analysis of gene expression distributions and their spatial patterns within tissue. Clustering or spatial domain detection represents an essential methodology for ST data, facilitating the exploration of spatial organizations with shared gene expression or histological characteristics. Traditionally, clustering algorithms for ST have focused on individual tissue sections. However, the emergence of numerous contiguous tissue sections derived from the same or similar tissue specimens within or across individuals has led to […]
- by Raza, Y., Moorthi, S., Yu, G., Chiappone, S., Vacchi-Suzzi, C., Luberto, C.Sphingomyelin Synthase 1 (gene name: SGMS1) participates in regulation of sphingolipid levels by synthesizing sphingomyelin from ceramide and phosphatidylcholine. Evidence have supported SGMS1's functions in regulating proliferation, cell cycle, cell death and migration. While its functions have begun to be explored, very little is known about upstream regulators. Here, we demonstrate that SGMS1 is a direct gene target of the GATA1-TAL1 transcriptional complex in K562 erythroleukemic cells. A predicted GATA1 consensus DNA binding sequence was identified with in a newly […]
- by Cuesta, C., Alcon-Perez, M., Zheng, J., Procel, N., Cota, R. R., Fennema, D., Rosell, A., Meson, D. L., Martinez-Castedo, B., Arafat, Y., Sanz-Fraile, H., Rajeeve, V., Alonso, D., Hynds, R. E., Swanton, C., Alcaraz, J., Cutillas, P., Reyes-Aldasoro, C. C., Wang, H., Castellano, E.Cancer-associated fibroblasts (CAFs) are key regulators of the tumor microenvironment, promoting tumor progression through extracellular matrix (ECM) remodeling and paracrine signaling, but the signaling pathways controlling CAF function remain incompletely defined. Here, we demonstrate that RAS-PI3K signaling plays a central role in CAF activation and ECM remodeling by promoting collagen crosslinking, fibronectin organization, and glycoprotein deposition at least partially through the activation of YAP. Disruption of RAS-PI3K interaction in CAFs leads to structurally and mechanically defective ECMs that impair tumor […]
- by Liu, F., Qian, J., Ma, C.Central Nervous System (CNS) tumors have sophisticated tumor microenvironment (TME) with different cell types such as astrocytes, microglia, neurons, vascular endothelial cells and immune cells. These non-cancerous cells orchestrate the brain TME to regulate cancer progression and therapeutic response. This study aimed to develop a cell composition deconvolution method for CNS tumor and to determine the impact of these cell compositions on patients outcomes. We identified the cell type-specific CpG loci using the pairwise differential methylation analysis for 13 major […]
- by Jepp, T. B. C., Christian, S., Dindot, S.Antisense oligonucleotides (ASOs) are chemically modified single-stranded oligonucleotides used to modulate the expression or processing of a target RNA transcript. The development of ASOs to treat human disease requires extensive preclinical studies in animal models. A critical component of these studies is determining the concentration of the ASO in tissues and biofluids, which are used to estimate the distribution, half-life, and dose-response relationship. The methods used to quantify ASOs are often constrained by low sensitivities, poor dynamic ranges, and the […]
- by Xu, Y., Zhou, H., Wu, X., Cui, W., Xu, S., He, X., Xiang, D., Zhou, M., Hong, L.The lamina joint is a critical determinant of leaf angle and crop architecture. While epidermal cells play a fundamental role in organ morphogenesis, influencing the overall shape and function of plants, their impact on lamina joint morphology has been largely overlooked. Here, we tracked the cellular dynamics of the rice lamina joint epidermis during leaf angle formation. We found that the asymmetric elongation between the lateral and medial edges, determined by spatial differences in the longitudinal elongation and number of […]
- by Holding, M. L., Disharoon, D., Haynes, L. M., Paruchuri, B. C., Golden, K., Shavit, J., Desch, K., Ginsburg, D., Sen Gupta, A., Cruz, Y. P., Drabeck, D.Interactions between predators and prey are often characterized by strong selection that shapes extreme physiological adaptations for survival in hostile environments. Venom resistance in large-bodied South American opossums (Clade Didelphini) provides a striking example as they are well known to prey upon snakes and have strong resistance to extremely toxic snake venom. While resistance is well known in this group of large-bodied opossums, relatively little is known about the venom resistance of the remaining diverse and speciose members of Didelphidae […]
- by Hirose, K., Umezu, S., Sato, D.A recent study by Kawatou et al. has shown that the local heterogeneity of ion channel conductance is a critical substrate for focal or reentrant arrhythmias. However, the role of fibroblasts with repolarization heterogeneity in the initiation and maintenance of arrhythmias remains unknown. In this study, we investigated how diffuse fibrosis contributes to the formation of focal and reentrant arrhythmias under drug-induced heterogeneity using physiologically detailed mathematical models of the human heart. To simulate drug-induced heterogeneity, we varied the maximum […]
- by Ingram, E. C., Altenritter, M. E., Wilson, K., Frisk, M. G., McCartin, K. R.An understanding of age-specific habitat requirements and the timing of critical ontogenetic transitions is essential to informing conservation and recovery efforts for Atlantic Sturgeon (Acipenser oxyrinchus). However, these are often difficult to assess due to the species' cryptic nature and the consequent lack of temporal and spatial habitat data across life stages. Sampling and microchemistry analysis of dorsal scute apical spines (i.e., dorsal scutes) represents an innovative methodology to reconstruct past life-history events of endangered populations of Atlantic Sturgeon. Here, […]
- by Shahnazari, P., Kavousi, K., Khorram Khorshid, H. R., Goliaei, B., Salek, R.Integrating multiple omics modalities is a crucial strategy in cancer research, particularly in metabolomics, enabling early detection and detailed exploration of cancer biomarker signatures. This study evaluates five strategies for integrating metabolomics data from liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and nuclear magnetic resonance. Deep Transfer Learning and Multiple Kernel Learning demonstrated superior performance, significantly improving classification accuracy, sensitivity, and robustness compared to single-modality analyses. Deep Transfer Learning employed a custom autoencoder for feature extraction followed by artificial neural network […]
- by Ji, X., Zhou, X., Chen, T., Duan, C., Tian, W., Zhu, L., Ma, Y., Gao, L.The aging of the body is accompanied by a decline in tissue function, and this decline mainly stems from the aging of tissue stem cells. Therefore, they play a crucial role in the aging of the body.This study explores the biological characteristics of senescent hUCMSCs by establishing a replicative senescence model of hUCMSCs and a rapid senescence model induced by D – galactose (D-Gal), and analyzing the proliferative capacity, cell viability, cell cycle, pluripotency, and reactive oxygen species (ROS) levels […]
- by Li, Y., Xiong, Y., Wei, W.Mutations with a synergistic effect on tumorigenesis were positively selected during tumor evolution, showing a tendency to co-occur in cancer genomes. To systematically gain insight of tumorigenic crosstalk at the mutation level, we utilized the FP-Growth algorithm in frequent pattern mining to create an unbiased map of co-occurring mutations from clinical genome sequencing data. We identified 100,933 frequent co-occurring mutation pairs across 22 cancer types. The co-mutation pairs involving cancer driver genes highlighted potential mechanisms for collaborative tumor formation, suggesting […]